The focus of this research is to define the natural history of HPV infection and cervical neoplasia, particularly immunologic and other cofactors that explain why cervical HPV infection (a common sexually-transmitted disease) progresses in rare instances to high-grade neoplasia. Accompanying prevention research on HPV diagnostics attempts to improve cervical cancer screening, while projects on HPV immunology are on the forefront of worldwide etiologic and preventive vaccine development efforts (see closely associated HPV vaccines project). Several methodologic and long-term projects were completed in FY 2001. Extremely strong and prospective associations of risk of high-grade cervical intraepithelial neoplasia were associated with infection with cancer-associated HPV types, based on data from the Costa Rican and Portland cohort studies. Improved cytologic and HPV DNA test methods were validated as part of the enrollment phase of the Costa Rican cohort, a 10,000-woman random sample of a high-risk province of Costa Rica. Much of the natural history work in the next few years will derive from the follow-up data from this cohort. Serologic projects continue to demonstrate the HPV-type specificity of the new tests based on synthesized virus-like particles now available for major cancer-associated types. Methods research continues on identifying and validating biomarkers of risk of progression given infection, and of possible protective immunity to HPV infection that might be useful for the proposed Phase 3 prophylactic trial against HPV 16 infection (see associated HPV vaccines project).